Typical nitration syntheses apply so-called "mixed acid", a mixture of concentrated nitric acid and sulfuric acids. This mixture produces the nitronium ion, which is the active species in aromatic nitration. This active ingredient, which can be isolated in the case of nitronium tetrafluoroborate, also effects nitration without the need for the mixed acid. In mixed-acid syntheses sulfuric acid is not consumed and hence acts as a catalyst as well as an absorbent for water. In the case of nitration of benzene, the reaction is conducted at a warm temperature, not exceeding 50 °C. The process is one example of electrophilic aromatic substitution, which involves the attack by the electron-rich benzene ring: Alternative mechanisms have also been proposed, including one involving single electron transfer.
Scope
Selectivity can be a challenge in nitrations because as a rule more than one compound may result but only one is desired, so alternative products act as contaminants or are simply wasted. Accordingly, it is desirable to design syntheses with suitable selectivity; for example, by controlling the reaction conditions, fluorenone can be selectively trinitrated or tetranitrated. The substituents on aromatic rings affect the rate of this electrophilic aromatic substitution. Deactivating groups such as other nitro groups have an electron-withdrawing effect. Such groups deactivate the reaction and directs the electrophilic nitronium ion to attack the aromatic meta position. Deactivating meta-directing substituents include sulfonyl, cyano groups, keto, esters, and carboxylates. Nitration can be accelerated by activating groups such as amino, hydroxy and methyl groups also amides and ethers resulting in para and ortho isomers. The direct nitration of aniline with nitric acid and sulfuric acid, according to one source, results in a 50/50 mixture of para- and meta-nitroaniline isomers. In this reaction the fast-reacting and activating aniline exists in equilibrium with the more abundant but less reactive anilinium ion, which may explain this reaction product distribution. According to another source, a more controlled nitration of aniline starts with the formation of acetanilide by reaction with acetic anhydride followed by the actual nitration. Because the amide is a regular activating group the products formed are the para and ortho isomers. Heating the reaction mixture is sufficient to hydrolyze the amide back to the nitrated aniline. In the Wolffenstein–Böters reaction, benzene reacts with nitric acid and mercury nitrate to give picric acid.
Ipso nitration
With aryl chlorides, triflates and nonaflates ipso substitution can take place as well in so-called ipso nitration. The phrase was first used by Perrin and Skinner in 1971 in an investigation into chloroanisole nitration In one protocol, 4-chloro-n-butylbenzene is reacted with sodium nitrite in t-butanol in the presence of 0.5 mol% Pd23, a biarylphosphine ligand and a phase-transfer catalyst to 4-nitro-n-butylbenzene.
